Scabies, caused by the mite Sarcoptes scabiei that burrows in the stratum corneum of the skin, is an important worldwide health problem affecting 300 million persons. In the U.S., scabies is common in the general population and frequently occurs in nursing homes and day care centers. Scabies persists despite the availability of toxic acaricides largely because carriers of the disease are asymptomatic and not diagnosed and treated. Our long-term objectives are to develop (1) a vaccine for immunization of susceptible populations for the global control of scabies and (2) better early diagnostic measures for ordinary scabies to reduce the likelihood of transmission. Prerequisite to the development of a vaccine and better diagnostic measures is understanding the immune response mechanism to scabies. To achieve these long-term objectives, the specific aims of the proposed research are: 1. Elucidate the key elements of the immune response mechanisms, mechanisms of resistance and possible immune modulation of the host by the parasite. 2. Establish the effector mechanisms responsible for elimination of an infestation in hosts that express resistance. 3. To identify the immunogenic components that will induce protective immunity to scabies. Aims 1 and 2 will be accomplished by monitoring the up and/or down regulation of key cytokine mediators by principal effector cells (e.g. macrophages, keratinocytes, Langerhans cells, T and B lymphocytes) in the immune response mechanism to Sarcoptes scabiei. The concentrations of several key cytokines will be determined in supernatants of cultures or isolated immune effector cells in the presence or absence of scabies mite products or extracts. In addition, the immune response presented by resistant hosts will be investigated to identify the mechanism responsible for resistance to scabies. Aim 3 will be achieved by conducting a series of vaccination trials using mite extracts or purified relevant antigens with the goal of inducing immune-based resistance.